In-vivo autologous bladder muscular wall regeneration: application of tissue-engineered pericardium in a model of bladder as a bioreactor

Abstract

Purpose: Tissue-engineered pericardium (TEP) is a collagen-rich matrix that has previously been shown to promote in vivo and in vitro tissue regeneration. We evaluated the potential of TEP as a source for the in-vivo creation of bladder muscular wall grafts. We used bladder wall as a bioreactor to create a natural environment for cellular growth and differentiation.

Materials and methods: Sixteen rabbits were divided into four groups. A control group underwent classical bladder autoaugmentation. Other groups underwent insertion of TEP between bladder mucosa and muscular layer: group 2 with insertion of TEP, group 3 with TEP over autologous bladder muscular wall fragments, and group 4 with autologous bladder smooth muscle cells (SMCs) seeded on TEP. After 4 and 8 weeks, grafts were biopsied for histopathological evaluations.

Results: Frames from groups 3 and 4 demonstrated more organized muscular wall generation with a significantly higher number of CD34 + endothelial progenitor cells and CD31 + microvessels, and maintenance of α-smooth muscle actin expression through immunohistochemistry. Group 4 showed significant enhancement of SMC penetration to TEP. Although the fragment-seeded group required a simpler procedure, the cell-seeded group showed superior organization of the muscular layer on histopathology. We found a semi-organized muscular layer and new vessels in the margins of TEP in group 3, while there was a homogeneous pattern of SMCs and new vessels in both the margins and center of TEP in group 4.

Conclusions: This preliminary work has important functional and clinical implications, as it indicates that use of the autologous SMC seeding method may enhance the properties of TEP in terms of bladder wall regeneration.